LINE-1 (L1) retrotransposons are active elements in the genome capable of mobilization in neuronal precursor cells, resulting in a mosaic in the brain. Upon mobilization, L1 insertions can alter gene expression, resulting in a genetic heterogenic population of neurons. The first aim of this proposal is to identify genomic loci of L1s in the human brain as compared to somatic tissues from the same individual in order to map and characterize de novo insertions in the brain. The second aim is to attenuate L1 retrotransposition in a mouse model and thereby investigate the functional significance of L1 in behavior. PUBLIC HEALTH RELEVANCE: The goal of this proposal is to characterize the activity and effects of mobile genetic elements in the germ and neural genomes. We will determine where in the genome the mobile elements insert and separately determine the functional consequences of the mobile elements on behavior of individuals. The outcome of this study will increase our understanding of human diversity and behavior and may contain insights into the genesis of multiple neurological diseases.